Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells

Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study,...

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Published in:International journal of molecular sciences 2022-10, Vol.23 (19), p.11890
Main Authors: Li, Jun-Kui, Sun, Hai-Tao, Jiang, Xiao-Li, Chen, Yi-Fei, Zhang, Zhu, Wang, Ying, Chen, Wen-Qing, Zhang, Zhang, Sze, Stephen Cho Wing, Zhu, Pei-Li, Yung, Ken Kin Lam
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Antitumor activity
Apoptosis
Autophagy
Cancer
Cancer therapies
Cell cycle
Cell growth
Cell proliferation
Chemical compounds
Chemotherapy
Colorectal cancer
Colorectal carcinoma
Cytotoxicity
Janus kinase 2
Kinases
Liver cancer
Pathogenesis
Pharmacology
Proteins
Saponins
Stat3 protein
TOR protein
Tumors
Western blotting
Xenografts
Xenotransplantation
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Summary:Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231911890